Overexpression of active TGF-beta-1 in the murine knee joint: evidence for synovial-layer-dependent chondro-osteophyte formation
Overexpression of active TGF-beta-1 in the murine knee joint: evidence for synovial-layer-dependent chondro-osteophyte formation
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DOI：
10.1053/joca.2000.0368
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发表时间：
2001-02-01
影响因子：
7
通讯作者：
van den Berg, WB
中科院分区：
文献类型：
--
作者：
Bakker, AC;van de Loo, FAJ;van den Berg, WB
目的：为了研究体内滑膜衬里细胞对软骨和韧带关节结构的长期和恒定的活性TGF-β表达的影响。设计：腺病毒载体AdTGF-β 1（223.225）用于C57 B1/6小鼠膝关节中活性TGF-β 1的过表达。结果发现，滑膜衬里层产生的生理相关水平的活性TGF-β 1导致组织病理学变化：滑膜增生和软骨-滑膜连接处的软骨-骨赘形成。关节内注射空对照载体（AdDL 70 -3）或过表达潜伏性TGF-β 1（AdTGF-β 1）后未观察到组织学变化。在骨关节炎（OA）和类风湿性关节炎（RA）中产生TGF-β的主要部位是滑膜衬里层。为了解决TGF-β诱导的变化是否与滑膜衬里中的表达位点相关的问题，通过用包封氯膦酸盐的脂质体局部处理来耗尽滑膜衬里层。耗尽的衬里导致了一个戏剧性的变化TGF-β 1诱导的病理：显着减少软骨骨赘形成和细胞外基质的积累增加synovium.Conclusion：这项研究表明，过度表达的活性TGF-β 1在膝关节OA样变化的结果，并建议滑膜衬里细胞有助于软骨骨赘的形成。(C)2001年国际骨关节炎研究学会。
Objective: To investigate the impact of a prolonged and constant active TGF-beta expression by the synovial lining cells on cartilage and ligamentous joint structures in vivo.Design: An adenoviral vector (AdTGF-beta1(223.225)) was used for the overexpression of active TGF-beta1 in knee joints of C57B1/6 mice.Results: It was found that physiological relevant levels of active TGF-beta1 produced by the synovial lining layer resulted in histopathological changes: hyperplasia of synovium and chondro-osteophyte formation at the so-called chondro-synovial junctions. No histological changes were seen after intra-articular injection of an empty control vector (AdDL70-3) or by overexpression of latent TGF-beta1 (AdTGF-beta1). The predominant site of TGF-beta production in osteoarthritis (OA) and rheumatoid arthritis (RA) is the synovial lining layer. To address the question whether the TGF-beta -induced changes were related to the expression site in the synovial lining, the synovial lining layer was depleted by local treatment with liposomes encapsulating clodronate. Depletion of the lining resulted in a dramatic change of TGF-beta1-induced pathology: markedly reduced chondro-osteophyte formation and increased accumulation of extracellular matrix in the synovium.Conclusion: This study shows that overexpression of active TGF-beta1 in the knee joint results in OA-like changes and suggests the synovial lining cells contribute to the chondro-osteophyte formation. (C) 2001 OsteoArthritis Research Society International.